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How do cells cope with their environment? Deciphering mechanical processes at the cell surface leading to signalling events and the adaptation of cells to changes in the environment.
My research interests lie in the understanding the molecular and physical principles that govern processes at the plasma membrane of cells. Particularly, by which mechanisms the force generating machinery of the cell cortex, structural filaments and motor proteins, govern and regulate the mechanical properties of the cell membrane and dynamics of cell membrane components, and vice versa, how membrane organisation and signalling events feed-back to the regulation of the cortex machinery. These mechanisms, which in turn regulate cell motility and cell-cell interactions, underlie important, poorly-understood human diseases that constitute global health problems. The lab employs novel assays based on reconstituted membrane systems in combination with measurements on live cells using state of the art fluorescence microscopy and mechanical manipulation.
I moved from a physics background to discovering the underlying principles in cell biology. Like every physicist does, I try to simplify the multilayered complexity in biology through a minimal set of components that can sufficiently model and describe biological phenomena. The most intriguing question in biology for me is how cells understand their mechanical environments and convey these signals to the nuclei. Having this perspective, I did my Ph.D. in studying the mechanical characteristics of the nuclear membrane of stem cells under Dr. Farshid Mohammad-Rafiee (IASBS Zanjan) and in collaboration with Prof. Jacques Prost (Institut Curie) and Prof. G.V. Shivashankar (ETH Zurich). I joined the Koester lab as a postdoctoral fellow at the University of Warwick through an EPSRC-funded project to dig into actin dynamics. I aim to study how the actomyosin cortex deforms lipid membranes in a minimal system and how actin length and curvature distributions might play a role in mediating biological processes.
I am interested in studying the coronavirus replication mechanism. Specifically, my research focusses on the non-structural proteins nsp3, nsp4, and nsp6, which have previously been shown to be vital for the formation of a viral replication platform. Yet, the extent of their involvement and specific functions remains to be elucidated. Therefore, the aim is to explore the interaction of these non-structural proteins with synthetic lipid membranes to determine their role in membrane binding and membrane deformation. This can be achieved by using giant unilamellar vesicles and optical fluorescence microscopy techniques.
I am fascinated by the dynamic and self-organising nature of eukaryotic endomembrane system. Many of the key molecular players involved in regulating membrane trafficking processes have been identified, but how they come together in space and time, to carry out their roles, remains unknown. I am working on developing biophysical tools to advance our understanding of principles that control complex cellular events, with a focus on actin-membrane interactions, through reconstituting them within minimal biomimetic set-ups.
I am interested in gaining a deeper understanding of cell adhesion and cell biomechanics in the Ehlers-Danlos Syndromes (EDS) and Hypermobility Spectrum Disorders (HSD). It has been established that these conditions demonstrate an altered integrin profile with a defective extracellular matrix, yet the consequences of this on the biomechanical properties of EDS/HSD fibroblasts has not been explored. I wish to use live cell microscopic techniques in combination with the mechanical manipulation of single cells to gain a better understanding of the dynamic processes involved in maintaining tissue integrity.
I am interested in understanding the dynamics of adherence junctions during cancer metastasis using an artificial system of polymer-lipid complex of different stiffness.
The main focus of my PhD project is on cell-cell adhesions, in particular septate junctions. Septate junctions are cellular junctions present in Drosophila melanogaster, which are known to be homologues to tight junctions in mammalian cells and are essential to maintain cell polarity and required for the proper functioning of epithelial tissue.
My PhD project is focused on studying spatial and temporal organization of septate junctions throughout embryonic development. This will be achieved in collaboration with my supervisor from Singapore, Dr Walter Hunziker. In Singapore, I will use APEX2 mediated proximity biotinylation and electron microscopy combined with proteomics studies. I will also characterize fine tuning role of extracellular matrix deposited by macrophages and tissue mechanics in the formation of these junctions. The success of this project will result in major advances in our understanding of the dynamic regulation of cell-cell adhesions and molecular details of a process integral for fly development.
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I am a postdoc interested in how physics influences biology. I started at the University of Hull where I received my MChem degree in Chemistry before I secured a place at the University of Birmingham on the Physical Sciences for Health CDT. Here I achieved my MSc and my PhD. I moved to the University of Warwick for my first post doc under Orkun Soyer where I focussed my attention into getting experience in biological lab practices. I am currently working on developing a vein-on-a-chip model to understand the physical parameters which influence deep vein thrombosis. I am using microfluidics and fluorescence microscopy to visualise flow through a biomimetic device to better determine where clots are likely to form within the venous geometry. I also aim to gain experience in developing giant unilamellar particles and alter their adhesiveness to advance my vein on a chip model and better understand thrombus formation.
The primary aim of my research is to experimentally validate long-standing questions and theoretical models pertaining to mediation of morphological changes in lipid membranes by a lipid anchored actin network. This will enable a better understanding of how the cell cortex can facilitate critical cellular functions, such as cell migration and cell division (in healthy cells and metastasising cells), as well as invasion by pathogenic bacteria and viruses. To this end, we use several imaging techniques, such as lattice light sheet microscopy, and a range of biophysical techniques to probe deformations of lipid membranes in giant unilamellar vesicles.
A 1min description of our research...
Resource for reconstitution of cytoskeletal systems. (2022), JoVE
Palani et al. (2021) Calponin-homology domain mediated bending of membrane associated actin filaments.
eLife, doi: 10.7554/eLife.61078.
Mosby et al. (2020) Visualization of myosin II filament dynamics in remodeling acto-myosin networks with interferometric scattering microscopy.
Biophys. J., doi: 0.1016/j.bpj.2020.02.025.
Ditlev et al. (2019) A Composition-Dependent Molecular Clutch Between T Cell Signaling Clusters and Actin.
eLife, doi: 10.7554/eLife.42695.
Köster et al. (2016) Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer.
PNAS, doi: 10.1073/pnas.1514030113.
Sinha, Köster et al. (2011) Cells Respond to Mechanical Stress by Rapid Disassembly of Caveolae.
Cell, doi: 10.1016/j.cell.2010.12.031.